title: HIV-1 drug-resistance patterns among patients on failing treatment in a large number of European countries.
abstract: BACKGROUND
  Information about patterns of HIV-1 drug resistance among treatment-exposed patients is crucial for the development of novel effective drugs. Currently no system exists that monitors patterns of resistance in patients failing therapy.
  
  
  METHODS
  The study included 1,988 HIV-1 sequences from patients experiencing therapy failure collected between 2000 and 2004 in 15 European countries. Genotypic resistance was interpreted using the ANRS algorithm. Phenotypic resistance was predicted using the Virco geno- to phenotype system.
  
  
  RESULTS
  80.7% of the sequences included at least one drug-resistance mutation. Mutations were found for NRTIs (73.5%), NNRTIs (48.5%), and protease inhibitors (35.8%). Ninety percent of sequences with genotypic resistance harbored M184V, M41L, K103N, D67N, and/or T215Y. Among NRTIs, resistance was most frequently predicted for lamivudine. About half of all sequences had reduced susceptibility for NNRTIs. Resistance to most boosted protease inhibitors was found in < 25%. No sequence had resistance to all currently available drugs.
  
  
  CONCLUSIONS
  Levels of resistance among patients with therapy failure were high. The patterns of resistance reflect resistance to drugs available for a longer time. Fully suppressive regimens can be designed even for the most mutated HIV because boosted protease inhibitors have remained active against most circulating viruses and new drug classes have become available.
authors.affiliation: Dept. of Virology, Erasmus MC, Rotterdam University Medical Centre, Rotterdam, the Netherlands. vandevijver@erasmusmc.nl
authors.forename: D A M C
authors.initials: DA
authors.lastname: van de Vijver
authors.forename: A M J
authors.initials: AM
authors.lastname: Wensing
authors.forename: B
authors.initials: B
authors.lastname: Åsjö
authors.forename: M
authors.initials: M
authors.lastname: Bruckova
authors.forename: L B
authors.initials: LB
authors.lastname: Jorgensen
authors.forename: R
authors.initials: R
authors.lastname: Camacho
authors.forename: A
authors.initials: A
authors.lastname: Horban
authors.forename: M
authors.initials: M
authors.lastname: Linka
authors.forename: M
authors.initials: M
authors.lastname: Lazanas
authors.forename: C
authors.initials: C
authors.lastname: Loveday
authors.forename: E
authors.initials: E
authors.lastname: MacRae
authors.forename: C
authors.initials: C
authors.lastname: Nielsen
authors.forename: D
authors.initials: D
authors.lastname: Paraskevis
authors.forename: M
authors.initials: M
authors.lastname: Poljak
authors.forename: E
authors.initials: E
authors.lastname: Puchhammer-Stöckl
authors.forename: L
authors.initials: L
authors.lastname: Ruiz
authors.forename: J-C
authors.initials: JC
authors.lastname: Schmit
authors.forename: G
authors.initials: G
authors.lastname: Stanczak
authors.forename: M
authors.initials: M
authors.lastname: Stanojevic
authors.forename: A-M
authors.initials: AM
authors.lastname: Vandamme
authors.forename: J
authors.initials: J
authors.lastname: Vercauteren
authors.forename: M
authors.initials: M
authors.lastname: Zazzi
authors.forename: L
authors.initials: L
authors.lastname: Bacheler
authors.forename: P
authors.initials: P
authors.lastname: Lecocq
authors.forename: J
authors.initials: J
authors.lastname: Villacian
authors.forename: C A B
authors.initials: CA
authors.lastname: Boucher
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D024882:Drug Resistance, Viral / Q000235:genetics*; D005060:Europe; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020539:Sequence Analysis, Protein; D017211:Treatment Failure
chemical_list: D017320:HIV Protease Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease